ATF4 and Alzheimer disease: Evidence suggests that PERK is directly responsible for cognitive impairment in AD patients (Duran-Aniotz et al., 2014), and both the activation of PERK (Lin et al., 2018) and ATF4 expression (Chen et al., 2003) have been shown to impair the transcriptional activity of CREB, leading to synaptic plasticity inhibition.